The expression of transforming growth factor alpha (TGF-alpha) is consistently associated with the malignant transformation of oral mucosal tissues in both hamster and human. The cheek pouch of the Syrian hamster represents an ideal model to elucidate the role of TGF-alpha in epithelial cancer development. A prerequisite for such investigations at the molecular level is to obtain hamster-specific TGF-alpha molecular probes. Here we report the successful cloning of the hamster TGF-alpha cDNA from a hamster oral cancer cell line (HCPC-1) by the polymerase chain reaction technique using synthetic oligonucleotide primers based on human TGF-alpha cDNA sequence. Analysis of the nucleotide sequence of the newly isolated hamster cDNA encoding the portion of the mature TGF-alpha peptide revealed that it is 92.6% (139/150) homologous to that of the rat and 93.3% (140/150) homologous to that of the human sequences. The predicted hamster TGF-alpha amino acid sequence is 96% (48/50) similar to that of human, while 94% (47/50) similar to that of rat. Using this hamster TGF-alpha cDNA as a probe, molecular hybridization experiments revealed that it detects hamster TGF-alpha mRNA with approximately 40 times and approximately 5 times greater sensitivity than similar probes from human and rat origin respectively. This hamster TGF-alpha cDNA should be of great value as a probe to evaluate the role of TGF-alpha in the normal and pathological processes using the hamster as an experimental model.